Myosin 1D and the branched actin network control the condensation of p62 bodies
Myosin 1D and the branched actin network control the condensation of p62 bodies
复制标题
肌球蛋白 1D 和分支肌动蛋白网络控制 p62 体的凝结
DOI：
10.1038/s41422-022-00662-6
复制
发表时间：
2022-04-27
期刊：
影响因子：
44.1
通讯作者：
Mi, Na
中科院分区：
文献类型：
--
作者：
Feng, Xuezhao;Du, Wanqing;Mi, Na
由液-液相分离(LLP)驱动的生物分子缩合是无膜细胞器在许多关键途径中组装的关键。细胞结构或成分如何在时空上调节LLP和凝析油的形成在很大程度上是未知的。在这里，我们揭示了细胞骨架动力学可以控制p62小体的凝聚，包括自噬适配器p62/SQSTM1和多泛素化的Cargo。分支肌动蛋白网络与p62小体相关，是其凝聚所必需的。肌球蛋白1D是一种分支的肌动蛋白相关的马达蛋白，它沿着分支的肌动蛋白网络推动小的纳米尺度的p62小体结合成大的微米尺度的凝聚体。在细胞模型和肌球蛋白1D基因敲除小鼠中，肌动蛋白细胞骨架网络的损伤损害了p62小体的凝聚，并通过自噬延缓了底物的降解。LLP支架与细胞骨架系统的偶联可能代表了细胞对相凝聚过程施加时空控制的一般机制。
Biomolecular condensation driven by liquid-liquid phase separation (LLPS) is key to assembly of membraneless organelles in numerous crucial pathways. It is largely unknown how cellular structures or components spatiotemporally regulate LLPS and condensate formation. Here we reveal that cytoskeletal dynamics can control the condensation of p62 bodies comprising the autophagic adaptor p62/SQSTM1 and poly-ubiquitinated cargos. Branched actin networks are associated with p62 bodies and are required for their condensation. Myosin 1D, a branched actin-associated motor protein, drives coalescence of small nanoscale p62 bodies into large micron-scale condensates along the branched actin network. Impairment of actin cytoskeletal networks compromises the condensation of p62 bodies and retards substrate degradation by autophagy in both cellular models and Myosin 1D knockout mice. Coupling of LLPS scaffold to cytoskeleton systems may represent a general mechanism by which cells exert spatiotemporal control over phase condensation processes.